Increasing importance of proton therapy

Increasing importance of proton therapy
Waldemar Ulmer
Strahlentherapie Nordwürttemberg and MPI of Physics, Göttingen, Germany

Cite this article as: Ulmer W. Increasing importance of proton therapy. Jour Proton Ther. 2015;1:112.

Scientific Note

1. Basic problems: protons versus heavy carbons

During the past decade, many proton therapy facilities have been established or are planned to become available very soon. Thus it is amusing that in the meantime much more vendors of proton treatment machines offer these facilities than corresponding machines working either with bremsstrahlung or fast electrons. Many researchers in the field of radiotherapy have expressed the opinion that about 20 % of malign tumors can be better treated with protons due to the rapid fall-off behind the Bragg peak than with the conventional radiotherapy with ultra-hard photons or electrons. Thus the normal tissue can be better protected by this behavior, whereas photons may travel long distances behind the target.

However, this overall situation is not so simple as it may appear, since there are still some open questions, and it should be mentioned that three important points have to be considered in detail:

1. Radiotherapy with ultra-hard bremsstrahlung between 6 MV and 15 MV has brought some essential improvements due to recent developments and progresses of IMRT/IGRT, Rapid Arc (VMAT) and Stereotaxy. These novel techniques have also provided better tumor control compared to older techniques like conformal radio-therapy or simple opposing fields, and it appears that these techniques now have most widely passed.

2. The RBE of radiotherapy with γ-quanta is per definition '1', where Co60 is used as the reference standard. On the other hand, research centers having now for a long period clinical experience with protons point out that the corresponding RBE of protons is also only '1' or slightly more, if the dose per fraction is assumed to be between 1.8 Gy and 2 Gy or a little bit higher as usual in the conventional radiotherapy with photons, e.g. integrated boosts in IMRT or Rapid Arc (VMAT). Therefore the principal advantage of proton therapy would only exist in the improved protection of normal tissue behind the target due the mentioned properties of the Bragg peak or SOBP. However, this aspect does not appear to be sufficiently explored, since the improved protection of normal tissue should enable to administer doses behind the shoulder of radiobiological dose-effect curves. With regard to protons there is only experience with high dose Stereotaxy, but this modality is already established since a long time in photon-radiotherapy.

3. Since radiotherapy with protons is not the only modality with regard to the application of positively charged particles, the nomenclature 'hadron therapy' has been established in order to denote besides protons also therapy modalities with neutrons, α-particles, heavy carbons C612, etc. In spite of the relatively high RBE the neutron therapy in general failed because of some severe shortcomings like the control of the beam-line. However, if one compares the Bragg curve of protons with that of heavy carbons, one should expect a Bragg peak about 36 times higher than that of protons, since according to Bethe-Bloch equation (BBE) the charge q of the projectile appears as the square (q2 = 36 for C612 versus q2 = 1 for protons)1,2. This behavior is, in fact, not true, and there exists a principal reason for the obvious discrepancy, as analyzed in previous studies, which may be verified from Figures 1‒3. Thus according to these figures based on previous investigations all positively charged projectile particles show besides energy transfer to environmental electrons via collision interaction a concurrence behavior after sufficient slowing down, namely the capture of electrons. This behavior implies that the effective charge qeff of a proton at the Bragg peak is slightly lower than 1, i.e. for mono-energetic protons qeff = 0.995, whereas for heavy carbons qeff amounts to 1.19. When one compares real Bragg curves of heavy carbons with those of protons, one may verify that the height of the Bragg peak of heavy carbons is increased by a factor 1.4 - 1.8, i.e. the Bragg curve is significantly steeper in this domain due to its mass factor 12 reducing energy straggling and lateral scatter drastically.

The dynamical behavior of heavy carbons from C6+ to C+ and finally to the neutral carbon, where all electronic shells are filled, can be characterized as a cascade procedure. Behind the Bragg peak the effective charge qeff tends to 0 for all positively charged hadrons and the LET significantly decreases to finally assume 0!

However, a comparison of a well-know proton Bragg curve with Figure 2 (heavy carbon) yields a large tail in Figure 2 resulting from fragments of numerous nuclear reactions. The angular distribution of such a tail of secondary fragments represents an additional aspect of heavy carbon radiotherapy, which is often not accounted for. If we further consider the high costs of this modality compared to the proton modality, it appears that the benefit of heavy carbons is not yet clearly determined, and only in Japan and Germany installations of this therapy modality exist.

Figure 1: LET for mono-energetic protons (dots) and overall stopping power S(z) of carbon ions 400 MeV/nucleon.

Figure 2: Measurement (HIMAC) and theoretical calculation of the Bragg curve of carbon ions (290 MeV/nucleon).

Figure 3: Effective charge qeff(E) of carbon ions in dependence of  the initial energy E0 for the cases E0 = 200, 300 and 400 MeV/nucleon. Independent of the initial energy of the carbon ion the effective charge is decreasing to finally become 0. Protons and α-particles behave in the same manner.

2. Sophisticated therapy planning systems

According to the LET of protons in the Bragg peak region one might expect a similar high RBE, which is, however, not true. Thus the electron capture effect, which yields to a decrease of LET behind the peak, may be one reason. This effect implies that RBE can only refer to an overall behavior. In more sophisticated planning systems the dynamical behavior of LET before and behind the Bragg peak should be accounted for. A first study of biological effects of protons and secondary particle has been published elsewhere.3

A secondary property of proton irradiation, which appears to be underrated in planning systems and even in the Monte-Carlo code GEANT44, represents the release of neutrons. Thus very low proton energies are able to perform a nuclear reaction of the form (restriction to the oxygen nucleus):

This reaction results from an exchange of a π- meson between oxygen and the positively charged proton. The exchange interaction occurs due to the Pauli Principle. The reaction isotope F916 undergoes a ß+ decay.

In general, the released neutron does not travel in forward direction. However, compared to heavy carbons, the release of neutrons and other secondary particles does not represent a severe obstacle in proton radiotherapy.

Conflict of Interest

The author declares that he has no conflict of interest. The author alone is responsible for the content and writing of this article.


  1. Ulmer W. Notes of the editorial board on the role of m medical physics in radiotherapy. Int J Cancer Ther Oncol. 2013;1:01014. [CrossRef]
  2. Ulmer W. The Role of Electron capture and energy exchange of positively charged particles passing through Matter. J Nucl and Particle Phys. 2012;2:77-86. [CrossRef]
  3. Paganetti H. Nuclear interactions in proton therapy dose and relative biological effect distributions origination from primary and secondary particles. Phys Med Biol. 2002;4:747-62. [CrossRef]
  4. Ulmer W. A new calculation formula of the nuclear cross-section of therapeutic protons. Int J Cancer Ther Oncol. 2014;2:020211. [CrossRef]

Submission: April 23, 2015; First Revision: April 26, 2015; Acceptance: April 26, 2015; Publication: April 27, 2015

Corresponding author: Waldemar Ulmer, PhD; Strahlentherapie Nordwürttemberg and MPI of Physics, Göttingen, Germany.

©Ulmer. Published by EJourPub. Journal of Proton Therapy. All rights reserved.

Copyright (c) 2015 Waldemar Ulmer

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